Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships

Adela Mendoza, Silvia Pérez-Silanes, Miguel Quiliano, Adriana Pabón, Silvia Galiano, Germán González, Giovanny Garavito, Mirko Zimic, Abraham Vaisberg, Ignacio Aldana, Antonio Monge, Eric Deharo

Research output: Contribution to journalArticle

Abstract

Piperazine and pyrrolidine derivatives were synthesised and evaluated for their capacity to inhibit the growth of Plasmodium falciparum chloroquine-resistant (FCR-3) strain in culture. The combined presence of a hydroxyl group, a propane chain and a fluor were shown to be crucial for the antiplasmodial activity. Five compounds of the aryl-alcohol series inhibited 50% of parasite growth at doses ≤10μM. The most active compound 1-(4-fluoronaphthyl)-3-[4-(4-nitro-2-trifluoromethylphenyl)piperazin-1-yl] propan-1-ol was almost 20-40 times more active on P. falciparum (IC50: 0.5μM) than on tumorogenic and non-tumorogenic cells. In vivo it has a very weak effect; inhibiting 35% of parasite growth only, at 10mg/kg/day against Plasmodium berghei infected mice without any impact on survival time. In silico molecular docking study and molecular electrostatic potential calculation revealed that this compound bound to the active site of Plasmodium plasmepsin II enzyme.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalExperimental Parasitology
Volume128
Issue number2
DOIs
StatePublished - Jun 2011

Keywords

  • Antimalarial agents
  • Antiplasmodial
  • Docking studies
  • Piperazine
  • Plasmodium
  • Pyrrolidine

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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  • Cite this

    Mendoza, A., Pérez-Silanes, S., Quiliano, M., Pabón, A., Galiano, S., González, G., Garavito, G., Zimic, M., Vaisberg, A., Aldana, I., Monge, A., & Deharo, E. (2011). Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships. Experimental Parasitology, 128(2), 97-103. https://doi.org/10.1016/j.exppara.2011.02.025